Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.     

Fiber Reinforced Laminates: Progressive Damage Modeling Based on Failure Mechanisms

In the present article, computational modeling of progressive damage in continuous fiber reinforced laminates is considered. After a general review of modeling approaches and experimentally observed behavior of laminates, the focus is laid on predicting non-linear laminate behavior by models based on continuum damage mechanics. The wide variety of continuum damage models is demonstrated by example of three different damage models from the literature which are described in more detail. Finally, a ply level damage model developed by the authors is presented. The model is based on brittle failure mechanisms postulated by Puck and is able to capture several characteristics of the damage behavior of laminates. Furthermore, this brittle damage model is extended to include plastic shear deformations. It is shown, that the extended model capturing brittle damage and plastic strains leads to significant improvements in the prediction of the non-linear laminate behavior.     

Flexible data anonymization using ARX—Current status and challenges ahead

The race for innovation has turned into a race for data. Rapid developments of new technologies, especially in the field of artificial intelligence, are accompanied by new ways of accessing, integrating, and analyzing sensitive personal data. Examples include financial transactions, social network activities, location traces, and medical records. As a consequence, adequate and careful privacy management has become a significant challenge. New data protection regulations, for example in the EU and China, are direct responses to these developments. Data anonymization is an important building block of data protection concepts, as it allows to reduce privacy risks by altering data. The development of anonymization tools involves significant challenges, however. For instance, the effectiveness of different anonymization techniques depends on context, and thus tools need to support a large set of methods to ensure that the usefulness of data is not overly affected by risk-reducing transformations. In spite of these requirements, existing solutions typically only support a small set of methods. In this work, we describe how we have extended an open source data anonymization tool to support almost arbitrary combinations of a wide range of techniques in a scalable manner. We then review the spectrum of methods supported and discuss their compatibility within the novel framework. The results of an extensive experimental comparison show that our approach outperforms related solutions in terms of scalability and output data quality—while supporting a much broader range of techniques. Finally, we discuss practical experiences with ARX and present remaining issues and challenges ahead.     

Integrating Robotic Fabrication in the Design Process

Does the application of robotic technologies in Southeast Asian cities, where the residential high-rise is pre-eminent, provide a unique opportunity to introduce bespoke design elements and liberate the high-rise from serial production and standardisation? Michael Budig, Jason Lim and Raffael Petrovic of the Future Cities Laboratory (FCL) at the Singapore-ETH Centre for Global Environmental Sustainability (SEC) introduce the research project ‘Design of Robotic Fabricated High Rises’ (2012-13) led by Fabio Gramazio and Matthias Kohler, exploring high-rise typologies and architectural scenarios for future vertical cities.     

Review of micro- and nanoplastic contamination in the food chain

Whereas the dramatic environmental impact of plastic waste rightfully receives considerable attention by scientists, policy makers and public in general, the human health impact of micro- and nanoplastics contamination of our food and beverages remains largely unknown. Indeed, most studies aim at understanding the environmental impact rather than the human health impact of a possible exposure to micro- and nanoplastics. In addition, these papers generally lack a methodological, standardised approach. Furthermore, some studies focus on the damage to and contamination level of animal species collected from the wild environment, and others investigate the rate and biology of microplastic uptake of animals fed with microplastics in laboratory. This review aims at understanding human exposure. Since there is, with few exceptions, no evidence available on the presence of micro- and nanoplastics in a normal diet, this study takes an indirect approach and analyses peer-reviewed publications since 2010 that document the presence of micro- and nanoplastics in those animals (more than 200 species) and food products that are part of the human food chain and that may thus contribute directly or indirectly to the uptake of micro- and nanoplastics via the human diet. It also addresses the question of the definitions, the methodologies and the quality criteria applied to obtain the reported results. This review suggests that, beyond a few estimations and comparisons, precise data to assess the exact exposure of humans to micro- and nanoplastics through their diet cannot be produced until standardised methods and definitions are available.     

Ferrocenyl‐Aryl Based trans‐Chelating Diphosphine Ligands: Synthesis,Molecular Structure and Application in Enantioselective Hydrogenation

Potentially trans‐chelating diphosphine ligands based on a ferrocenyl‐aryl backbone were synthesised in a four‐step sequence and the molecular structures in the solid state of two representatives were determined by X‐ray diffraction. High throughput screening of these ligands in rhodium‐, ruthenium‐ and iridium‐mediated hydrogenations of a variety of alkenes and ketones revealed that these ligands can deliver high enantioselectivity for alkenes (up to 98% ee) but are less selective when ketones are used as the substrates. The coordination behaviour of one ligand in its square planar palladium and platinum dichloride complexes was studied by ³¹P NMR and only trans‐chelated complexes, together with oligomeric by‐products, were observed. Reaction with the (p‐cymene)ruthenium dichloride dimer, [RuCl₂(p‐cymene)]₂, resulted in a mixture of diastereomeric complexes.     

Constitutive ply damage modeling, FEM implementation, and analyses of laminated structures

The present work is concerned with the modeling of progressive damage in fiber reinforced polymer laminates and its implementation into a finite element code as constitutive material law. The objective is to predict damage evolution and material degradation due to matrix dominated failure modes (“matrix cracking”). In a previous work, a ply-level continuum damage model based on ply failure mechanisms postulated by Puck has been presented. This model predicts the evolution of the complete tensor of elasticity for the damaged material and is able to capture the effects of stiffness recovery and slanted cracking under transverse compression. In the current work, this damage model is adapted for arbitrary loading paths and implemented within the finite element method in order to analyze complex structures and study their damage behavior including load redistribution due to damage. To demonstrate some key features and the application of the damage model in structural analysis, it is applied in a single element analysis as well as in the simulation of Open Hole Compression tests for which results are compared to experimental data from the literature.     

The use of thermoluminescent detectors for measurements of proton dose distribution

Slowing down spectra, LET spectra, hit probabilities, and radiation doses were simulated for the interaction of single 218Po and 214Po alpha particles with sensitive basal and secretory cell nuclei in the bronchial epithelium of human and rat lungs for defined exposure conditions. Probabilities per unit track length for transformation, derived from in vitro experiments with C3H 10T1/2 cells, were used to estimate transformation probabilities for randon progeny alpha particles in basal and secretory cells. Different weighting schemes were assumed to relate cellular hit probabilities, doses and transformation probabilities, obtained for different cell depths and airway generations, to lung cancer risk per unit exposure. In vitro transformation and in vivo lung cancer incidence were simulated by a state-vector model which provides a stochastic formulation of dose-rate dependent cellular transitions related to formation of double strand breaks, repair, inactivation, stimulated mitosis and promotion through loss of intercellular communication.     

Effect of Partially Fluorinated N‐Alkyl‐Substituted Piperidine‐2‐carboxamides on Pharmacologically Relevant Properties

The modulation of pharmacologically relevant properties of N‐alkyl‐piperidine‐2‐carboxamides was studied by selective introduction of 1–3 fluorine atoms into the n‐propyl and n‐butyl side chains of the local anesthetics ropivacaine and levobupivacaine. The basicity modulation by nearby fluorine substituents is essentially additive and exhibits an exponential attenuation as a function of topological distance between fluorine and the basic center. The intrinsic lipophilicity of the neutral piperidine derivatives displays the characteristic response noted for partially fluorinated alkyl groups attached to neutral heteroaryl systems. However, basicity decrease by nearby fluorine substituents affects lipophilicities at neutral pH, so that all partially fluorinated derivatives are of similar or higher lipophilicity than their non‐fluorinated parents. Aqueous solubilities were found to correlate inversely with lipophilicity with a significant contribution from crystal packing energies, as indicated by variations in melting point temperatures. All fluorinated derivatives were found to be somewhat more readily oxidized in human liver microsomes, the rates of degradation correlating with increasing lipophilicity. Because the piperidine‐2‐carboxamide core is chiral, pairs with enantiomeric N‐alkyl groups are diastereomeric. While little response to such stereoisomerism was observed for basicity or lipophilicity, more pronounced variations were observed for melting point temperatures and oxidative degradation.